The absolute bioavailability of an oral sustained-release formulation of desvenlafaxine succinate in healthy subjects

Abstract

Background/Aims To assess the absolute bioavailability of sustained-release desvenlafaxine succinate (DVS-SR) and pharmacokinetics of desvenlafaxine (DV) in healthy subjects. Methods In this single-dose, open-label, 2-period crossover study, subjects were randomized to receive either a 1× 100-mg oral tablet of DVS-SR or a single 50 mg/1 hr intravenous (IV) infusion of desvenlafaxine succinate (DVS) in each period. Plasma was assayed for the total racemic mixture (R+S) and ratio (R/S) of DV. The absolute bioavailability was calculated from oral and IV AUC values of the racemic mixture of DV. Results A total of 14 subjects were enrolled and completed the study. DVS-SR was generally well tolerated. There were no clinically important changes in routine laboratory tests, vital signs measurements, and electrocardiograms (ECG). The 50-mg IV formulation had a higher Cmax (232 ng/mL) than the 100-mg oral formulation (160 ng/mL). The half-lives were similar, ranging from 14 to 15 hours, and the 100-mg oral formulation of DVS-SR had a higher overall exposure (AUCoral 3996 vs AUCIV 2443 ng*h/mL). The absolute bioavailability of the oral formulation was 80.5%. The concentration profiles for R and S enantiomers were approximately equivalent to each other for both the IV and oral formulations. Conclusion DVS-SR provided good oral bioavailability (80.5%) and an evenly balanced enantiomeric ratio. Clinical Pharmacology & Therapeutics (2005) 77, P47–P47; doi: 10.1016/j.clpt.2004.12.071